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    Summary
    EudraCT Number:2011-001161-41
    Sponsor's Protocol Code Number:BRF113928
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-05-15
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2011-001161-41
    A.3Full title of the trial
    A Phase II study of the BRAF inhibitor dabrafenib as a single agent and in combination with the MEK inhibitor trametinib in subjects with BRAF V600E mutation positive metastatic (stage IV) non-small cell lung cancer
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to test a new drug for treating non-small cell lung cancer
    A.4.1Sponsor's protocol code numberBRF113928
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorNovartis Pharma Services AG
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Pharmaceuticals UK Limited
    B.5.2Functional name of contact pointMedica Information Services
    B.5.3 Address:
    B.5.3.1Street Address200 Frimley Business Park
    B.5.3.2Town/ cityFrimley, Camberley
    B.5.3.3Post codeGU16 7SR
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44 1276 698370
    B.5.6E-mailmedinfo.uk@novartis.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tafinlar
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxoSmithKline trading Services Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDabrafenib
    D.3.2Product code GSK2118436
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDabrafenib
    D.3.9.1CAS number 1195765-45-7
    D.3.9.2Current sponsor codeGSK2118436
    D.3.9.3Other descriptive nameN-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-fluorophenyl}-2,6-difluorobenzene sulfonamide, methanesulfonate salt
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Tafinlar
    D.2.1.1.2Name of the Marketing Authorisation holderGlaxoSmithKline trading Services Ltd
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDabrafenib
    D.3.2Product code GSK2118436
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNDabrafenib
    D.3.9.1CAS number 1195765-45-7
    D.3.9.2Current sponsor codeGSK2118436
    D.3.9.3Other descriptive nameN-{3-[5-(2-Amino-4-pyrimidinyl)-2-(1,1-dimethylethyl)-1,3-thiazol-4-yl]-2-luorophenyl}-2,6-difluorobenzene sulfonamide, methanesulfonate salt
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTrametinib
    D.3.2Product code GSK1120212
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTRAMETINIB
    D.3.9.1CAS number 871700-17-3
    D.3.9.2Current sponsor codeGSK1120212
    D.3.9.3Other descriptive nameN-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]- 6,8-dimethyl-2,4,7-trioxo-
    D.3.9.4EV Substance CodeSUB119776
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTrametinib
    D.3.2Product code GSK1120212
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTRAMETINIB
    D.3.9.1CAS number 871700-17-3
    D.3.9.2Current sponsor codeGSK1120212
    D.3.9.3Other descriptive nameN-[3-[3-cyclopropyl-5-[(2-fluoro-4-iodophenyl)amino]- 6,8-dimethyl-2,4,7-trioxo-
    D.3.9.4EV Substance CodeSUB119776
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced non-small cell lung cancer and BRAF mutations
    E.1.1.1Medical condition in easily understood language
    Lung cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the overall response rate (ORR) in subjects with stage IV BRAF V600E mutant non-small cell lung cancer administered dabrafenib as a single agent (Cohort A) and in combination with trametinib (Cohorts B and C)
    E.2.2Secondary objectives of the trial
    • To assess progression-free survival (PFS), duration of response and overall survival (OS) in subjects with stage IV BRAF V600E mutant nonsmall cell lung cancer administered dabrafenib as a single agent (Cohort A) and in combination with trametinib (Cohorts B and C)
    • To further characterize the safety and tolerability of dabrafenib
    when administered as a single agent and in combination with
    trametinib to subjects with stage IV BRAF V600E mutant nonsmall
    cell lung cancer
    • To characterize the population pharmacokinetics and identify
    important determinants of variability of dabrafenib as a single agent (Cohort A) and in combination with trametinib (Cohorts B and C)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Subjects eligible for enrolment in the study and previously enrolled subjects crossing over from monotherapy to combination therapy must meet all of the following criteria:
    1. Signed written informed consent;
    2. Histologically- or cytologically-confirmed diagnosis of NSCLC stage IV (according to AJCC Staging 7th Edition);
    3. For Cohorts A and B, documented tumor progression (based on radiological imaging) after receiving at least one prior approved platinum-based chemotherapy regimen for advanced stage/metastatic NSCLC. An alternate chemotherapeutic agent/regimen is an acceptable substitute in the event that the subject was intolerant to, or ineligible to receive platinum based chemotherapy. Subjects enrolled in Cohort B cannot have more than 3 prior systemic treatments for advanced stage/metastatic NSCLC (neoadjuvant and adjuvant therapies are not counted in number of prior regimens and maintenance therapy is not counted as a separate regimen). Subjects in Cohort C will be required to have not received prior systemic anti-cancer therapies for metastatic disease (i.e., dabrafenib/trametinib will be 1st line treatment for metastatic disease);
    4. Measurable disease according to RECIST v1.1 [Eisenhauer, 2009]. Refer to Section 7.2.3.1 for the definition of a measurable lesion;
    5. Male or female ≥18 years of age;
    6. Anticipated life expectancy of at least 3 months;
    7. Presence of a BRAF V600E mutation in lung cancer tissue. Mutation must be locally confirmed in a CLIA-certified laboratory (or equivalent). An adequate amount of umor tissue (archived tumor tissue, or fresh biopsy if archived tissue is not available) must be available at the time of enrolment for central validation of BRAF mutation see Section 7.1.1 for testing details and requirements regarding central confirmation);
    8. Able to swallow and retain oral medication;
    9. Women of childbearing potential must have a negative serum pregnancy test within 14 days before the first dose of study treatment and agree to use effective contraception, as defined in Section 7.4, during the study;
    NOTE: Oral contraceptives are not reliable due to potential drug-drug interaction with dabrafenib
    10. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2 [Oken, 1982];
    11. Must have adequate baseline organ function as definedin Table 1:
    Hematologica
    ANC ≥ 1.5 × 109/L
    Hemoglobin ≥ 9 g/dL
    Platelet count ≥ 100 x 109/L
    PT/INRb and PTT ≤ 1.5 x ULN
    Hepatic
    Total bilirubin ≤ 1.5 x ULN
    AST and ALT ≤ 2.5 x ULN
    Renal (at least one of the following):
    Serum creatininec ≤ 1.5 mg/dL
    Creatinine clearancec ≥ 50 mL/min
    Cardiac
    Left Ventricular Ejection fraction (LVEF)d ≥ LLN by ECHO
    12. French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
    13. Previously tested for presence of EGFR and ALK mutations in lung cancer tissue confirmed in a CLIA-certified laboratory (or equivalent). Subjects with EGFR or ALK mutation are eligible if they have previously received EGFR or ALK inhibitor(s) respectively.
    E.4Principal exclusion criteria
    Subjects eligible for enrolment in the study and previously enrolled subjects crossing over from monotherapy to combination therapy must not meet any of the following criteria:
    1. Previous treatment with a BRAF inhibitor (including but not limited to dabrafenib, vemurafenib, LGX818, and XL281/BMS-908662) or MEK inhibitor (including but not limited to trametinib, AZD6244, and RDEA119) prior to start of study treatment
    (Note: Prior treatment with dabrafenib is allowed for crossover subjects in Cohort A);
    2. Anti-Cancer therapy including chemotherapy, radiation-therapy, immunotherapy, biologic therapy or major surgery within 14 days prior to start of study treatment (Note: Dabrafenib monotherapy within 14 days prior to starting combination therapy
    is allowed for crossover subjects in Cohort A);
    3. Use of any investigational anti-cancer drug within 14 days or 5-half-lives (minimum 14 days), prior to start of study medication (Note: Dabrafenib monotherapy within 14 days prior to starting combination therapy is allowed for crossover subjects in Cohort
    A);
    4. Current use of a prohibited medication or expected to require any of thesemedications during treatment with study treatment (See Section 6.2);
    5. Unresolved toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 (NCI CTCAE v4.0) [NCI, 2009] Grade 2 or higher from previous anti-cancer therapy, except alopecia;
    6. Presence of active gastrointestinal disease or other condition that will interfere significantly with the absorption of drugs. If clarification is needed as to whether a condition will significantly affect absorption of drugs, contact the GlaxoSmithKlne
    (GSK) medical monitor for guidance to enrol the subject;
    7. Known Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) infection. Subjects with laboratory evidence of cleared HBV and HCV infection may be enrolled;
    8. History of another malignancy < 3 years prior to starting study treatment or any malignancy with confirmed activating RAS-mutation;
    Exceptions: subjects with any of the following malignancies within 3 years (does not include malignancies with confirmed activating RAS-mutation) are eligible: (a) a history of completely resected skin cancer, (b) successfully treated in situ carcinoma,
    (c) chronic lymphocytic lymphoma (CLL) in stable remission, or (d) indolent prostate cancer (definition: clinical stage T1 or T2a, Gleason score ≤6, and prostate specific
    antigen [PSA] < 10 ng/mL) requiring no or only anti-hormonal therapy with histologically confirmed tumour lesions that can be clearly differentiated from lung cancer target and non-target lesions are eligible
    9. Subjects with brain metastases are excluded if their brain metastases are:
    • Symptomatic OR
    • Treated (surgery, radiation therapy) but not clinically and radiographically stable 3 weeks after local therapy(as assessed by contrast enhanced magnetic resonance imaging [MRI] or computed tomography [CT]), OR
    • Asymptomatic and untreated but >1 cm in the longest dimension
    10. A history or evidence of cardiovascular risk including any of the following:
    • Corrected QT (QTc) interval ≥480 msecs
    • History of acute coronary syndromes (including myocardial infarction or unstable angina) within 6 months prior to first dose of study treatment
    • Coronary angioplasty, or stenting within the past 24 weeks;
    • A history or evidence of current Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) guidelines;
    • Treatment refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mmHg which cannot be controlled by antihypertensive therapy;
    • Abnormal cardiac valve morphology (≥Grade 2) documented by echocardiogram (subjects with Grade 1 abnormalities [i.e., mild regurgitation/stenosis] can be entered on study). Subjects with moderate valvular thickening should not be entered on study;
    • Patients with intra-cardiac defibrillators
    • A history or evidence of current clinically significant uncontrolled arrhythmias; Exception: Subjects with atrial fibrillation controlled for > 30 days prior to randomization are eligible.
    11. Uncontrolled medical conditions (i.e., diabetes mellitus, hypertension, etc.), psychological, familial, sociological, or geographical conditions that interfere with the subject’s safety or obtaining informed consent or do not permit compliance with the protocol; or unwillingness or inability to follow the procedures required in the protocol;
    12. Pregnant, or actively breastfeeding females.
    13. Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to the study treatments, their excipients, and/or dimethyl sulfoxide (DMSO)
    Additional Exclusion Criteria for combination therapy (Cohorts B and C as well as subjects that crossover from monotherapy to combination therapy) please refer to page 34 of the protocol for further information
    E.5 End points
    E.5.1Primary end point(s)
    ORR, which is defined as the percentage of subjects with a
    confirmed complete response (CR) or partial response (PR) by
    investigator assessment as per RECIST v1.1 criteria
    E.5.1.1Timepoint(s) of evaluation of this end point
    Scans are every 6 weeks from Week 1-36, then every 12 weeks after Week 36.
    E.5.2Secondary end point(s)
    • PFS defined as the interval between first dose and the
    earliest date of disease progression or death due to any cause
    • Duration of response, defined for the subset of subjects with
    confirmed CR or PR, as the time from first documented evidence
    of CR or PR until time of first documented disease progression or death due to any cause
    • OS defined as the time from first dose until death due to any cause
    • Measurements used to evaluate safety will include physical and
    dermatological examinations, ophthalmic examination, vital
    signs, 12-lead ECGs, ECHO, clinical laboratory tests, and AEs
    • Dabrafenib and trametinib population pharmacokinetic
    parameters such as apparent clearance (CL/F) and volume of
    distribution (V/F), and relevant covariates which may influence
    exposure (e.g. age, weight, or disease related covariates)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Scans are every 6 weeks from Week 1-36, then every 12 weeks after Week 36.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over Yes
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA30
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    France
    Germany
    Italy
    Korea, Republic of
    Netherlands
    Norway
    Spain
    Taiwan
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The study will be considered completed when progression of disease has occurred in all patients Cohorts B and C, a minimum of 70% of subjects have died in each cohort, or 5 years have passed since the last subject’s first dose, whichever comes first. Subjects who are still benefiting from study treatment at the time of study completion may continue to receive study treatment by an alternate mechanism (such as roll-over study, commercial product or a post-trial patient effort).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 40
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 60
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 50
    F.4.2.2In the whole clinical trial 100
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    All subjects who permanently discontinue study medication will be followed for survival and new anti-cancer therapy until study completion. Subjects who are still benefiting from GSK2118436 at the time of study completion may have the option to enter the rollover study, Protocol BRF114144, an open-label, rollover study of GSK2118436.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-05-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-09-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-04-26
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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